Risk Factors and Susceptibility in Gonococcal Infection

淋球菌感染的危险因素和易感性

基本信息

项目摘要

DESCRIPTION (provided by applicant): Three-quarters of men and one-quarter of women who are exposed to a partner infected with Neisseria gonorrhoae do not become infected. Resistance to experimental infection in men is correlated with the presence of serum IgG antibodies directed against Paraglobosyl lipooligosaccharides (LOS); 4-5% of male soldiers develop these antibodies during natural infection. In a study of STD Clinic clientele, we found that serum concentrations of Paraglobosyl LOS IgG were higher in those who had had prior gonococcal infections than in those who had not. There was a threshold of LOS IgG above which no clients reported to the STO Clinics with active gonococcal infections, either at the time the sera were drawn or over several years of follow-up. This threshold was present in 10-15% of individuals in the Baltimore core mixing population. The risk of exposure experienced by the clients during follow up was not known. In order to test the hypothesis that Paraglobosyl LOS IgG contributes to resistance to gonococcal infection, we need to determine serum Paraglobosyl IgG concentrations at or near the time of exposure. We propose recruiting the partners of STD clients with active gonococcal infections as soon as they are identified. We will measure concentrations of Paraglogosyl LOS IgG in the serum and cervical secretions (women) of partners and determine whether they are infected. We will find out whether concentrations of serum or local LOS IgG are higher in contacts of patients who resist infection than in those who do not. We will use RT-PCR of polyG tracts of gonococci in Gram stained exudates to find out which LOS molecules are present during transmission. We will compare local and systemic LOS IgG among symptomatic and asymptomatic, but infected, patients and contacts. Two other variables may confound the interpretation of data in women: whether their genital epithelial cells constitutively express CEACAM and whether their vaginal flora include lactobaccilli that produce H2O2. Ligation of CEACAM by gonococci leads to bacterial death, in vitro. Only ca. 30% of women constitutively express CEACAM; constitutive CEACAM expression may lower the risk of acquiring infection following exposure. We will compare constitutive CEACAM expression and lactobacilli colonization among women who do and do not become infected after exposure. We will use bacterial vaginosis as a surrogate for the absence of H2O2-expressing lactobacilli. The results of these studies will expand our understanding of resistance to gonococcal infection and may provide the basis for the development of a Paraglobosyl LOS vaccine that, if sufficiently immunogenic, could prevent gonococcal transmission among those at highest risk for infection.
描述(由申请人提供):接触感染淋病奈瑟菌的伴侣,四分之三的男性和四分之一的女性没有被感染。男性对实验性感染的抵抗与血清中存在针对副lolobosyl lipooligosaccharides (LOS)的IgG抗体相关;4-5%的男性士兵在自然感染期间产生这些抗体。在性病诊所的一项研究中,我们发现血清副lobosyl LOS IgG浓度在那些有过淋球菌感染的人高于那些没有感染过淋球菌的人。有一个LOS IgG的阈值,超过这个阈值,在抽取血清时或在几年的随访中,没有客户报告患有活动性淋球菌感染。在巴尔的摩核心混合人群中,有10-15%的个体存在这一阈值。患者在随访期间所经历的暴露风险尚不清楚。为了验证副肺酰基LOS IgG有助于抵抗淋球菌感染的假设,我们需要在暴露时或接近暴露时测定血清副肺酰基IgG浓度。我们建议招募性传播疾病患者的合作伙伴与活跃的淋球菌感染一旦确定。我们将测量副paraglosyl LOS IgG在血清和宫颈分泌物中的浓度(女性)的合作伙伴,并确定他们是否感染。我们将查明抗感染患者接触者的血清或局部LOS IgG浓度是否高于抗感染患者接触者。我们将利用革兰氏染色渗出液中淋球菌多g小束的RT-PCR来发现哪些LOS分子在传播过程中存在。我们将比较有症状和无症状但感染的患者和接触者的局部和全身LOS IgG。另外两个变量可能会混淆对女性数据的解释:她们的生殖器上皮细胞是否组成性地表达CEACAM,以及她们的阴道菌群是否包括产生H2O2的乳酸杆菌。淋球菌结扎CEACAM可导致体外细菌死亡。只有约30%的女性表达CEACAM;本构性CEACAM表达可降低暴露后感染的风险。我们将比较暴露后感染和未感染的妇女的CEACAM组成表达和乳酸菌定植。我们将使用细菌性阴道病作为缺乏表达h2o2的乳酸菌的替代物。这些研究的结果将扩大我们对淋球菌感染耐药性的认识,并可能为开发Paraglobosyl LOS疫苗提供基础,这种疫苗如果具有足够的免疫原性,就可以防止淋球菌在感染风险最高的人群中传播。

项目成果

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JOHN McLeod GRIFFISS其他文献

JOHN McLeod GRIFFISS的其他文献

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{{ truncateString('JOHN McLeod GRIFFISS', 18)}}的其他基金

Phase I Clinical Trial Unit for Therapeutics Against Infectious Diseases
传染病治疗的 I 期临床试验单位
  • 批准号:
    8335319
  • 财政年份:
    2011
  • 资助金额:
    $ 18.41万
  • 项目类别:
PHASE I CLINICAL TRIAL UNIT FOR THERAPEUTICS AGAINST INFECTIOUS DISEASES
传染病治疗的 I 期临床试验装置
  • 批准号:
    8340145
  • 财政年份:
    2011
  • 资助金额:
    $ 18.41万
  • 项目类别:
PHASE I CLINICAL TRIAL UNIT FOR THERAPEUTICS AGAINST INFECTIOUS DISEASES
传染病治疗的 I 期临床试验装置
  • 批准号:
    8340147
  • 财政年份:
    2011
  • 资助金额:
    $ 18.41万
  • 项目类别:
Phase I Clinical Trial Unit for Therapeutics Against Infectious Diseases
传染病治疗的 I 期临床试验单位
  • 批准号:
    8335318
  • 财政年份:
    2011
  • 资助金额:
    $ 18.41万
  • 项目类别:
PHASE I CLINICAL TRIAL UNIT FOR THERAPEUTICS AGAINST INFECTIOUS DISEASES
传染病治疗的 I 期临床试验装置
  • 批准号:
    8340149
  • 财政年份:
    2011
  • 资助金额:
    $ 18.41万
  • 项目类别:
Phase I Clinical Trial Unit for Therapeutics Against Infectious Diseases
传染病治疗的 I 期临床试验单位
  • 批准号:
    8441449
  • 财政年份:
    2008
  • 资助金额:
    $ 18.41万
  • 项目类别:
Phase I Clinical Trial Unit for Therapeutics Against Infectious Diseases
传染病治疗的 I 期临床试验单位
  • 批准号:
    8441446
  • 财政年份:
    2008
  • 资助金额:
    $ 18.41万
  • 项目类别:
Phase I Clinical Trial Unit for Therapeutics Against Infectious Diseases
传染病治疗的 I 期临床试验单位
  • 批准号:
    8441448
  • 财政年份:
    2008
  • 资助金额:
    $ 18.41万
  • 项目类别:
Phase I Clinical Trial Unit for Therapeutics Against Infectious Diseases
传染病治疗的 I 期临床试验单位
  • 批准号:
    8656603
  • 财政年份:
    2008
  • 资助金额:
    $ 18.41万
  • 项目类别:
Phase I Clinical Trial Unit for Therapeutics Against Infectious Diseases
传染病治疗的 I 期临床试验单位
  • 批准号:
    8844892
  • 财政年份:
    2008
  • 资助金额:
    $ 18.41万
  • 项目类别:

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